Summary of work: Alzheimer's disease (AD) is the most widespread among several neurological degenerative diseases (dementias) that occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimer's disease follow the NINCDS-ADRDA criteria. Section investigators examined the relationship between age-related memory change and repeat testing using serial administrations of the California Verbal Learning Test (CVLT) in 385 nondemented Baltimore Longitudinal Study of Aging participants aged 55 and older with two or more memory assessments. In this study, we investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of learning and interference, short- and long-delay free and cued recall, and recognition hits in separate mixed-effects regressions. We found cross-sectional effects of age (p < 0.001) and sex (p < 0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. Longitudinal age changes were documented across total learning and long-delay free and cued recall regardless of baseline scores (p <= 0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on Trial 5, short-delay cued recall and recognition hits (p < 0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short- and long-delay recall such that younger baseline age was associated with improvement over time whereas older baseline age was associated with decline over time. These results suggest that there are longitudinal declines in CVLT performance in normal aging and these changes are influenced by baseline age. Furthermore, failure to account for the influence of repeat testing with aging may decrease sensitivity to detect pathologic decline. Section investigator also examined whether Alzheimer?s disease reflects a chronic process that begins many years before the clinical expression of dementia. In this study, we examined whether premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA). 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD. The relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period. These results suggest that a greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis. We examined the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.